神经节苷脂GM3在非酒精性脂肪肝炎小鼠肝脏中的表达变化  

Expression of ganglioside GM3 in the liver of mice with nonalcoholic steatohepatitis

作　　者：胡默然 吴周璐 赵晨曦 龚颖芸 周红文[1] HU Moran;WU Zhoulu;ZHAO Chenxi;GONG Yingyun;ZHOU Hongwen(Department of Endocrinology and Metabolism,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院内分泌科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2022年第2期153-159,共7页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81730094,31900832);江苏省科技厅自然科学青年基金(BK20191074)。

摘　　要：目的:探究高脂高糖饮食诱导的非酒精性脂肪肝炎(non-alcoholic steatohepatitis,NASH)小鼠模型较对照组肝脏内单唾液酸神经节苷脂3(monosialodihexosylganglioside,GM3)等鞘糖脂的变化。方法:16只6周龄C57BL/6J小鼠随机分为对照组和模型组,每组8只,对照组喂普通饲料,正常饮水;模型组喂高脂饲料,含糖饮水(23.1 g/L蔗糖+18.9 g/L葡萄糖)。检测两组小鼠血清生化指标丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST),采用HE染色观察两组小鼠肝脏组织病理变化。使用Exion UPLC-QTRAP 6500 PLUS(Sciex)液质联用仪,以电喷雾电离(ESI)模式进行脂质组学分析。采用独立样本t检验、曼-惠特尼检验进行组间差异的统计学分析。结果:①高脂高糖饮食喂养7个月组小鼠较普通饲料喂养组ALT、AST水平显著升高(P<0.05)。②模型组较对照组显著降低的指标有肝脏内总GM3(P=0.016)及GM3 d18:1/20:0(P=0.005)、GM3 d18:1/22:0(P=0.004)、GM3 d18:1/24:0(P=0.004)和GM3 d18:1/26:0(P=0.042),总神经酰胺、总乳糖神经酰胺等显著升高(P<0.05)。结论:高脂高糖饮食喂养的NASH模型小鼠肝脏中经乳糖神经酰胺向GM3转化的合成通路受阻。Objective:This study aims to investigate the changes of glycosphingolipid,especially the ganglioside GM3,in the liver of NASH model mice induced by high-fat and high-sugar diet.Methods:A total of 16 C57BL/6 J mice aged 6-weeks old were randomly allocated into control group and NASH group(control n=8;NASH n=8).Control mice were fed with a standard chow diet and water as control group,while the other mice were fed high fat diet accompanied by ad libitum consumption of water with high fructose and glucose content(23.1 g/L d-fructose+18.9 g/L d-glucose)to establish NASH models as model group.Serum levels of ALT and AST were measured to evaluate the pathological changes of liver tissues.Liver histology was assessed using HE stains in paraffin-embedded sections using standard commercially used methods.Liver lipidomics analysis was perfonned in an electrospray ionization mode using Exion UPLC-QTRAP 6500 PLUS(Sciex)LC/MS.The student’s t test and Mann-Whitney U test were used for statistical analysis.Results:①The levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in NASH mice were significantly higher than that in control group(P<0.05).②Compared with the control group,total GM3 and subtype species,including GM3 d18:1/20:0(P=0.005),GM3 d18:1/22:0(P=0.004),GM3 d18:1/24:0(P=0.004)and GM3 d18:1/26:0(P=0.042)were significantly lower in the model group,which were dignosed as NASH group based on the NAFLD activity score.Conversely,total ceramide and total lactosylceramide(LacCer)were remarkably elevated in NASH group than control group(P<0.05).Conclusion:The synthetic pathway from LacCer to GM3 is dampened in NASH model mice,which are established by high-fat and high-fructose diet.

关 键 词：NASH 神经节苷脂GM3 鞘糖脂 ST3GAL5 

分 类 号：R575.5[医药卫生—消化系统]